EP2389923B1 - Stabile, gebrauchsfertige, injizierbare Paracetamolformulierung - Google Patents

Stabile, gebrauchsfertige, injizierbare Paracetamolformulierung Download PDF

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Publication number
EP2389923B1
EP2389923B1 EP10005258A EP10005258A EP2389923B1 EP 2389923 B1 EP2389923 B1 EP 2389923B1 EP 10005258 A EP10005258 A EP 10005258A EP 10005258 A EP10005258 A EP 10005258A EP 2389923 B1 EP2389923 B1 EP 2389923B1
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EP
European Patent Office
Prior art keywords
paracetamol
stable aqueous
solution according
solution
group
Prior art date
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Active
Application number
EP10005258A
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English (en)
French (fr)
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EP2389923A1 (de
Inventor
Ioulia Tseti
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Uni Pharma Kleon Tsetis Pharmaceutical Laboratories SA
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Uni Pharma Kleon Tsetis Pharmaceutical Laboratories SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
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Priority to PL10005258T priority Critical patent/PL2389923T3/pl
Application filed by Uni Pharma Kleon Tsetis Pharmaceutical Laboratories SA filed Critical Uni Pharma Kleon Tsetis Pharmaceutical Laboratories SA
Priority to EP10005258A priority patent/EP2389923B1/de
Priority to ES10005258T priority patent/ES2403121T3/es
Priority to PT100052588T priority patent/PT2389923E/pt
Priority to SI201030168T priority patent/SI2389923T1/sl
Priority to DK10005258.8T priority patent/DK2389923T3/da
Priority to AP2012006597A priority patent/AP3151A/xx
Priority to UAA201214331A priority patent/UA104381C2/uk
Priority to MA35461A priority patent/MA34314B1/fr
Priority to CA2799666A priority patent/CA2799666C/en
Priority to BR112012029212-9A priority patent/BR112012029212A2/pt
Priority to RU2012151433/15A priority patent/RU2519764C1/ru
Priority to MYPI2012004801A priority patent/MY160458A/en
Priority to US13/695,785 priority patent/US8877817B2/en
Priority to PCT/EP2011/002482 priority patent/WO2011144335A1/en
Priority to HK13109609.9A priority patent/HK1182315B/xx
Priority to CN201180024241.4A priority patent/CN102985069B/zh
Publication of EP2389923A1 publication Critical patent/EP2389923A1/de
Priority to TNP2012000516A priority patent/TN2012000516A1/en
Priority to ZA2012/08605A priority patent/ZA201208605B/en
Application granted granted Critical
Publication of EP2389923B1 publication Critical patent/EP2389923B1/de
Priority to HRP20130184AT priority patent/HRP20130184T1/hr
Priority to CY20131100241T priority patent/CY1113999T1/el
Priority to SM201300038T priority patent/SMT201300038B/xx
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof

Definitions

  • the present invention refers to a pharmaceutical composition
  • a pharmaceutical composition comprising Paracetamol for parenteral administration by IV infusion, with an optimum pH 6.0 (ranging between 5.5 and 6.5) comprising at least one stabilizing-dissolving compound for paracetamol in solution selected from the group consisting of cyclodextrins, at least one stabilizing compound bearing at least one thiol functional group and at least one stabilizing compound selected from the group consisting of Thiamine salts in a suitable concentration, able to stabilize and solubilize the paracetamol even at elevated temperatures.
  • the present invention relates to an injectable liquid paracetamol composition according to claim 1, which is stable even at elevated temperatures over a longer period of time.
  • Paracetamol is considered to be the main active metabolite of phenacetin and acetanidile having analgesic and antipyretic properties. Paracetamol has equivalent analgesic and antipyretic action to that of aspirin whilst it expresses weak antiinflammatory action therefore its use in inflammatory rheumatic diseases is limited.
  • the secondary cause of degradation may be the deacetylation of the amino group generating p-aminophenol which is also quickly degraded producing p-benzoquinoneimine. This deacetylation takes places both at acid pH and (much faster) at basic pH once the phenolate form is present.
  • US Patent 6,028,222 discloses the use of free radical antagonists or free radical scavengers, which may be a polyol or an organic compound substituted by one or more thiol functional groups, to provide stable analgesic formulations of paracetamol.
  • US Patent 4,727,064 discloses the use of alkylated cyclodextrins to improve the solubility of drugs, inter alia paracetamol, in water.
  • the present invention therefore concerns a stable aqueous paracetamol solution for use in IV infusion comprising at least one stabilizing-dissolving compound for paracetamol in solution selected from the group consisting of cyclodextrins, at least one stabilizing compound bearing at least one thiol functional group and at least one stabilizing compound selected from the group consisting of Thiamine salts.
  • the at least one stabilizing-dissolving compound for paracetamol in solution selected from the group consisting of cyclodextrins, the at least one stabilizing compound bearing at least one thiol functional group and the at least one stabilizing compound selected from the group consisting of Thiamine salts are preferably present in a total concentration between 0.001% and 20 % m/v.
  • the stable aqueous paracetamol solution according to the invention may have a pH between 4.0 and 7.0.
  • the solution may be a buffer with a buffer composition selected from at least one of the acid form and the ionized form of: citric, malic, acetic, sorbic, phosphoric, fumaric, lactic, gluconic and tartaric acids or mixtures thereof.
  • the pH is between 5.5 and 6.5 and more preferably the pH is adjusted to 6.
  • a typical buffer includes phosphate or sodium citrate/acetate and is preferably disodium phosphate dihydrate.
  • the preferred cyclodextrin is a hydroxyalkyl-cyclodextrin, in particular 2-hydroxypropyl-beta-cyclodextrin.
  • the at least one stabilizing-dissolving compound for paracetamol in solution selected from the group consisting of cyclodextrins is provided in a concentration between 0.2% m/v and 19% m/v, preferably in a concentration between 0.2% m/v and 6.0% m/v and more preferably between 0.5% and 3.0% m/v.
  • the 2-hydroxypropyl beta-cyclodextrin is preferably selected from derivatives with a degree of substitution of between 2.5 and 10 hydroxypropyl substituents per beta-cyclodextrin molecule, more preferably between 3.5 and 8 hydroxypropyl substitutents per beta-cyclodextrin molecule.
  • the molar ratio of Paracetamol to 2-hydroxypropyl beta-cyclodextrin is preferably 100:1 to 0.1:1 , more preferably 5:1, most preferably 1.5:1.
  • the at least one stabilizing compound bearing at least one thiol functional group is selected from the group consisting of thioglycerols, cystein, acetylcycstein, thioglycolic acid and/ or salts thereof, dithiothreitol, reduced glutathione, thiolactic acid and/ or salts thereof, thiourea and mercaptoethanesulfonic acid and is typically a thioglycerol, preferably monothioglycerol, present in a concentration between 0.001% m/v and 0.2% m/v.
  • the at least one stabilizing compound selected from the group consisting of Thiamine salts is preferably Thiamine HCI and is preferably present in a concentration between 0.001% m/v and 0.2% m/v.
  • the aqueous solution may further comprise other chelating agents or complexing agents.
  • the chelating or complexing agent in solution may be selected from the group consisting of EDTA, nitrilotriacetic acid, ethylenediamine-N,N'-diacetic-N,N'-dipropionic acid, ethylenediamine-tetra(methylene phosphoric acid), 2,2' (ethylenediamino) -dibutyric acid, ethylene glycol bis(2-aminoethylether)-N,N,N',N'-tetra acetic acid, and/or salts thereof, and is preferably EDTA.
  • the chelating or complexing agent is present in a concentration between 0.001% m/v and 0.2% m/v.
  • the stable aqueous paracetamol solution according to the invention may further comprise isotonizing agents, preferably sodium chloride.
  • the stable aqueous paracetamol solution for IV infusion may be sterilized by heat or by filtration.
  • a typical concentration of paracetamol is between 0.20% and 10% m/v, preferably 0.5% and 1.5% m/v.
  • the aqueous medium of the solution according to the invention may have been deoxygenated by a water-insoluble inert gas (N 2 ).
  • compositions according to the invention will be administered intravenously and they are stable when stored for more than 24 months at room temperature. Moreover, the compositions may be even stable when stored for more than 30 days at elevated temperatures, for example 70°C.
  • a composition may be prepared in solution and stored in clear glass containers or bottles made of a polymer material such as polyethylene, or in soft material bags made from polyethylene, polyvinylchloride or polypropylene.
  • the molar ratio of Paracetamol to cyclodextrin is preferably 100:1 to 0.1:1 , more preferably 5:1 and most preferably 1.5:1.
  • the solution comprises 2 mg to 200 mg, preferably more than 5 mg, most preferably 10 mg Paracetamol per millilitre solution.
  • the complexing or chelating agent may comprise 0.001 to 5 mg, preferably 0.0015 to 1 mg, most preferably 0.1 mg per millilitre solution.
  • the solution comprises typically 2 mg to 150 mg, preferably more than 3 mg, most preferably between 6 mg and 7 mg cyclodextrin per millilitre solution.
  • the at least one stabilizing compound bearing at least one thiol functional group which is preferably monothioglycerol, may comprise 0.01 to 5 mg, preferably 0.015 to 1 mg, most preferably 0.1 mg per millilitre solution.
  • the at least one stabilizing compound selected from the group consisting of Thiamine salts which is preferably Thiamine HCl, may comprise 0.01 to 5 mg, preferably 0.015 to 1 mg, most preferably 0.1 mg per millilitre solution.
  • the solution is in the form of a unit dose that does not exceed 100 millilitres.
  • the inventor has found a way to prepare a stable aqueous solution comprising at least one stabilizing-dissolving compound for paracetamol in solution selected from the group consisting of cyclodextrins, at least one stabilizing compound bearing at least one thiol functional group and at least one stabilizing compound selected from the group consisting of Thiamine salts in a suitable concentration, which is not only capable of having a concentration of Paracetamol of more than 10 mg per millilitre of solution, but is also stable and does not need to be refrigerated when packed in clear glass sealed vials, or in stoppered glass vials or in bottles made of a polymer material such as polyethylene, or in soft material bags made from polyethylene, polyvinyl chloride or polypropylene.
  • “stable” is meant that the solution can be stored for at least 24 months at room temperature and at least 30 days at elevated temperature (70°C) without the appearance of colour and particulate matter which is visible to the eye.
  • the use of the stabilizing-dissolving and stabilizing compounds according to the invention and preferably the chelating agent has been found to not only increase the Paracetamol solubility to the extent that it is possible to dissolve 1000 mg of Paracetamol into a final volume of 100 ml but also effectively stabilises the solution preventing the formation of particulate matter and colour at elevated temperature in ampoules, vials and bags.
  • the solution may be formulated in unit dose form, each unit dose containing from 100 mg to 1500 mg Paracetamol inclusive, more preferably from 600 mg to 1000 mg inclusive, most preferably 1000 mg, in a volume not exceeding 100 millilitres.
  • the injectable stabilised solution of the invention may be prepared by methods known in the art.
  • the stabilised injectable solution of the invention may be packed into suitable containers known in the art (for example glass ampoules, vials, cartridges, glass sealed vials, or in stoppered glass vials or in bottles made of a polymer material such as polyethylene, or in soft material bags made from polyethylene, polyvinyl chloride or polypropylene).
  • suitable containers known in the art for example glass ampoules, vials, cartridges, glass sealed vials, or in stoppered glass vials or in bottles made of a polymer material such as polyethylene, or in soft material bags made from polyethylene, polyvinyl chloride or polypropylene).
  • the glass should preferably be clear glass.
  • the stabilized injectable solution of the invention is suitable for intravenous use.
  • the stabilized injectable solution of the invention need not be stored under refrigerated conditions to provide a shelf life of at least 24 months, saving refrigeration costs during transport and storage, and alleviating patient discomfort during administration.
  • a preferred pharmaceutical composition according to the invention comprises: Table 1: Ingredient Quantity/100 ml Paracetamol 1000 mg Hydroxypropyl-beta-cyclodextrin HPBCD 666 mg Monothioglycerol (MTG) 10 mg EDTA 10 mg Thiamine HCI 10 mg NaCI 600 mg Disodium phosphate dihydrate 35.6 mg Water for Injection to 100 ml Final pH (HCI or NaOH) 1M 5.5-6.5
  • Table 2 The unit composition of a second formulation (Control, comparative example) is provided in Table 2 below: Table 2: Ingredient Quantity/100 ml Paracetamol 1000 mg Hydroxypropyl-beta-cyclodextrin HPBCD 666 mg Monothioglycerol (MTG) 10 mg EDTA 10 mg NaCI 600 mg Disodium phosphate dihydrate 35.6 mg Water for Injection to 100 ml Final pH (HCl or NaOH) 1M 5.5-6.5
  • Tables 3-4 show stability evaluations of 1000 mg per 100 ml Paracetamol formulations and the solution according to the invention shows advantages over a control solution with a different composition of stabilizing compound.
  • the solution is stirred until all the MTG, EDTA, NaCI, Thiamine HCI and Disodium phosphate dihydrate is dissolved.
  • the pH is then adjusted to 6 with HCl 1M.
  • 100 g paracetamol is added to the solution and stirred until dissolved. pH is adjusted to 6, should it be required and made up to 100% volume with WFI.
  • the resultant 1000mg/100 ml paracetamol solution is sterilized by filtration with 0.22Pm filters and filled into presterilized vials or bags, under aseptic conditions. The vials or bags are sealed aseptically under nitrogen.
  • the formulation contains 1000 mg/100 ml paracetamol, as determined by validated HPLC.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (15)

  1. Stabile wässrige Paracetamol-Lösung zur Verwendung bei der IV-Infusion, umfassend mindestens eine stabilisierende-lösende Verbindung für Paracetamol in Lösung, die ausgewählt ist aus der Gruppe bestehend aus Cyclodextrinen, mindestens eine stabilisierende Verbindung, die mindestens eine funktionelle Thiol-Gruppe trägt, und mindestens eine stabilisierende Verbindung, die ausgewählt ist aus der Gruppe bestehend aus Thiamin-Salzen.
  2. Stabile wässrige Lösung nach Anspruch 1, bei der die mindestens eine stabilisierende-lösende Verbindung für Paracetamol in Lösung, die aus der Gruppe von Cyclodextrinen ausgewählt ist, die mindestens eine stabilisierende Verbindung, die mindestens eine funktionelle Thiol-Gruppe trägt, und die mindestens eine stabilisierende Verbindung, die ausgewählt ist aus der Gruppe bestehend aus Thiamin-Salzen, in einer Gesamtkonzentration zwischen 0,001 % und 20 % m/V vorliegen.
  3. Stabile wässrige Lösung nach Anspruch 1 oder 2, bei der die mindestens eine stabilisierende-lösende Verbindung für Paracetamol in Lösung ausgewählt ist aus der Gruppe bestehend aus Hydroxyalkyl-beta-cyclodextrinen.
  4. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 3, bei der die mindestens eine stabilisierende-lösende Verbindung für Paracetamol in Lösung 2-Hydroxypropyl-beta-cyclodextrin ist.
  5. Stabile wässrige Lösung nach irgendeinem der Ansprüche 1 bis 4, bei der die Konzentration der mindestens einen stabilisierenden-lösenden Verbindung für Paracetamol in Lösung zwischen 0,2% m/V und 19 % m/V, vorzugsweise zwischen 0,2 % m/V und 6,0 % m/V, insbesondere bevorzugt zwischen 0,5 % m/V und 3,0 % m/V liegt.
  6. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 5, bei der die mindestens eine stabilisierende Verbindung, die mindestens eine funktionelle Thiol-Gruppe trägt, ausgewählt ist aus der Gruppe bestehend aus Thioglycerolen, Cystein, Acetylcystein, Thioglycolsäure und/oder deren Salzen, Dithiothreit, reduziertem Glutathion, Thiomilchsäure und/oder deren Salzen, Thioharnstoff und Mercaptoethansulfonsäure.
  7. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 6, bei der die mindestens eine stabilisierende Verbindung, die mindestens eine funktionelle Thiol-Gruppe trägt, ein Thioglycerol, bevorzugt Monothioglycerol, ist.
  8. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 7, bei der die mindestens eine stabilisierende Verbindung, die mindestens eine funktionelle Thiol-Gruppe trägt, in einer Konzentration zwischen 0,001 % m/V und 0,2 % m/V vorliegt.
  9. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 6, bei der die mindestens eine stabilisierende Verbindung, die ausgewählt ist aus der Gruppe bestehend aus Thiamin-Salzen, Thiamin-HCl ist.
  10. Stabile wässrige Paracetamol-Lösung nach irgendeinem der Ansprüche 1 bis 9, bei der die mindestens eine stabilisierende Verbindung, die ausgewählt ist aus der Gruppe bestehend aus Thiamin-Salzen, in einer Konzentration zwischen 0,001 % m/V und 0,2 % m/V vorliegt.
  11. Stabile wässrige Paracetamol-Lösung nach irgendeinem der vorangehenden Ansprüche, weiter umfassend ein chelatisierendes Mittel.
  12. Stabile wässrige Paracetamol-Lösung nach Anspruch 11, bei der das chelatisierende Mittel ausgewählt ist aus der Gruppe bestehend aus EDTA, Nitrilotriessigsäure, Ethylendiamin-N,N'-diessig-N,N'-dipropionsäure, Ethylendiamin-tetra(methylenphosphorsäure), 2,2'-(Ethylendiamino)dibuttersäure, Ethyl-englycolbis(2-aminoethylether)-N,N,N',N'-tetraessigsäure und/oder deren Salzen und vorzugsweise EDTA ist.
  13. Stabile wässrige Paracetamol-Lösung nach Anspruch 11 oder 12, bei der das chelatisierende Mittel in einer Konzentration zwischen 0,001 % m/V und 0,2 % m/V vorliegt.
  14. Stabile wässrige Paracetamol-Lösung nach irgendeinem der vorangehenden Ansprüche, bei der der pH zwischen 4,0 und 7 liegt und die Lösung mit einer Puffer-Zusammensetzung gepuffert ist, die aus mindestens einer der SäureForm und der ionisierten Form von: Citronen-, Äpfel-, Essig-, Sorbin-, Phosphor-, Fumar-, Milch-, Glucon- und Weinsäuren oder deren Mischungen ausgewählt ist und vorzugsweise Dinatriumphosphatdihydrat ist.
  15. Stabile wässrige Paracetamol-Lösung nach irgendeinem der vorangehenden Ansprüche, bei der die Konzentration an Paracetamol zwischen 0,20 % und 10 % m/V, vorzugsweise zwischen 0,5 % und 1,5 % m/V beträgt.
EP10005258A 2010-05-19 2010-05-19 Stabile, gebrauchsfertige, injizierbare Paracetamolformulierung Active EP2389923B1 (de)

Priority Applications (22)

Application Number Priority Date Filing Date Title
EP10005258A EP2389923B1 (de) 2010-05-19 2010-05-19 Stabile, gebrauchsfertige, injizierbare Paracetamolformulierung
ES10005258T ES2403121T3 (es) 2010-05-19 2010-05-19 Formulación de paracetamol inyectable, estable, lista para usar
PT100052588T PT2389923E (pt) 2010-05-19 2010-05-19 Formulação injectável estável de paracetamol pronta a usar
SI201030168T SI2389923T1 (sl) 2010-05-19 2010-05-19 Stabilna, pripravljena za uporabo, injicirajoča paracetamol formulacija
DK10005258.8T DK2389923T3 (da) 2010-05-19 2010-05-19 Stabil klar til brug injicerbar paracetamol-formulering
PL10005258T PL2389923T3 (pl) 2010-05-19 2010-05-19 Trwały, gotowy do użycia iniekcyjny preparat paracetamolu
US13/695,785 US8877817B2 (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
MA35461A MA34314B1 (fr) 2010-05-19 2011-05-18 Préparation de paracétamol injectable stable, prête à l'emploi
CA2799666A CA2799666C (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
BR112012029212-9A BR112012029212A2 (pt) 2010-05-19 2011-05-18 formulação de paracetamol injetável pronta para o uso estável
RU2012151433/15A RU2519764C1 (ru) 2010-05-19 2011-05-18 Стабильная готовая к применению композиция парацетамола для инъекций
MYPI2012004801A MY160458A (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
AP2012006597A AP3151A (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
PCT/EP2011/002482 WO2011144335A1 (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
HK13109609.9A HK1182315B (en) 2010-05-19 2011-05-18 Stable ready to use injectable paracetamol formulation
CN201180024241.4A CN102985069B (zh) 2010-05-19 2011-05-18 稳定的随时可用的对乙酰氨基酚注射制剂
UAA201214331A UA104381C2 (uk) 2010-05-19 2011-05-18 Стабільна готова до застосування композиція парацетамолу для ін'єкцій
TNP2012000516A TN2012000516A1 (en) 2010-05-19 2012-10-29 Stable ready to use injectable paracetamol formulation
ZA2012/08605A ZA201208605B (en) 2010-05-19 2012-11-15 Stable ready to use injectable paracetamol formulation
HRP20130184AT HRP20130184T1 (hr) 2010-05-19 2013-03-04 Stabilni injekcijski oblik paracetamola spreman za uporabu
CY20131100241T CY1113999T1 (el) 2010-05-19 2013-03-22 Σταθερο ετοιμο προς χρηση ενεσιμο σκευασμα παρακεταμολης
SM201300038T SMT201300038B (it) 2010-05-19 2013-04-03 Formulazione di paracetamolo iniettabile stabile epronto per l'uso

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP10005258A EP2389923B1 (de) 2010-05-19 2010-05-19 Stabile, gebrauchsfertige, injizierbare Paracetamolformulierung

Publications (2)

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EP2389923A1 EP2389923A1 (de) 2011-11-30
EP2389923B1 true EP2389923B1 (de) 2013-01-30

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US (1) US8877817B2 (de)
EP (1) EP2389923B1 (de)
CN (1) CN102985069B (de)
AP (1) AP3151A (de)
BR (1) BR112012029212A2 (de)
CA (1) CA2799666C (de)
CY (1) CY1113999T1 (de)
DK (1) DK2389923T3 (de)
ES (1) ES2403121T3 (de)
HR (1) HRP20130184T1 (de)
MA (1) MA34314B1 (de)
MY (1) MY160458A (de)
PL (1) PL2389923T3 (de)
PT (1) PT2389923E (de)
RU (1) RU2519764C1 (de)
SI (1) SI2389923T1 (de)
SM (1) SMT201300038B (de)
TN (1) TN2012000516A1 (de)
UA (1) UA104381C2 (de)
WO (1) WO2011144335A1 (de)
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WO2024246565A2 (en) 2023-06-02 2024-12-05 Ioulia Tseti Pharmaceutical composition comprising ibuprofen

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ZA201300398B (en) * 2012-11-27 2013-09-25 Genfarma Laboratories S L Injectable liquid formulation of the combination of tramadol and paracetamol
WO2016008546A1 (en) * 2014-07-18 2016-01-21 Everbright Pharmaceuticals S.A.R.L. Aqueous formulation comprising paracetamol and ibuprofen
CN105797166A (zh) * 2016-03-30 2016-07-27 吉林长白山药业集团股份有限公司 用羟丙基环糊精包合对乙酰氨基酚制成液体制剂的方法
WO2018192664A1 (en) 2017-04-20 2018-10-25 Hyloris Developments Sa METHOD FOR PREPARING A COMPOSITION WITH A LOW DISSOLVED OXYGEN CONTENT, COMPRISING ACETAMINOPHEN, AND OPTIONALLY ONE OR MORE NSAIDs, AND A COMPOSITION OBTAINED THEREOF
WO2019180072A1 (en) 2018-03-22 2019-09-26 Bayer Pharma Aktiengesellschaft Parenteral pharmaceutical composition comprising neladenoson bialanate
US20230165928A1 (en) * 2020-04-30 2023-06-01 Blue Sky Innovation, Llc Compositions and methods comprising stable reduced glutathione
GR1010637B (el) * 2023-01-13 2024-02-15 Ιουλια Κλεωνος Τσετη Σταθερο υδατικο διαλυμα παρακεταμολης για χρηση σε ενδοφλεβια εγχυση

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WO2024246565A2 (en) 2023-06-02 2024-12-05 Ioulia Tseti Pharmaceutical composition comprising ibuprofen
GR1010809B (el) * 2023-09-13 2024-10-25 Ιουλια Τσετη Υδατικο διαλυμα ιβουπροφαινης παρακεταμολης για χρηση σε ενδοφλεβια χορηγηση

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SMT201300038B (it) 2013-07-09
WO2011144335A8 (en) 2012-12-06
US8877817B2 (en) 2014-11-04
BR112012029212A2 (pt) 2020-09-29
ZA201208605B (en) 2013-09-25
WO2011144335A1 (en) 2011-11-24
PT2389923E (pt) 2013-03-28
AP2012006597A0 (en) 2012-12-31
EP2389923A1 (de) 2011-11-30
CY1113999T1 (el) 2016-07-27
CN102985069B (zh) 2014-11-26
PL2389923T3 (pl) 2013-06-28
HRP20130184T1 (hr) 2013-05-31
CN102985069A (zh) 2013-03-20
TN2012000516A1 (en) 2014-04-01
CA2799666C (en) 2016-02-16
RU2519764C1 (ru) 2014-06-20
AP3151A (en) 2015-03-31
ES2403121T3 (es) 2013-05-14
DK2389923T3 (da) 2013-03-18
UA104381C2 (uk) 2014-01-27
US20130210922A1 (en) 2013-08-15
MY160458A (en) 2017-03-15
CA2799666A1 (en) 2011-11-24
MA34314B1 (fr) 2013-06-01
HK1182315A1 (en) 2013-11-29
SI2389923T1 (sl) 2013-06-28

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